How multimodal stimuli become integrated is a fundamental question in neuroscience. This question is particularly relevant to flavor perception, in which simultaneous stimulation of touch, temperature, taste and olfaction invariably occurs during ingestion. Functional imaging studies in humans have provided important insights into the neural bases of multimodal flavor integration, yet cannot address issues requiring higher resolution or experimental manipulation of neural activity or of flavor experience. To address these limitations, the goal of the present project is to establish a rat model for investigating the neural mechanisms of flavor integration. To determine whether retronasal olfaction occurs in rats as it does in humans, a first study will employ optical calcium imaging to measure spatio-temporal patterns evoked in the olfactory bulb by various behaviors associated with the oral ingestion of odorants by awake rats. The perceptual similarities between retro- and orthonasal odorants will simultaneously be investigated. To determine whether flavor integration occurs perceptually in rats, a second study will investigate whether conditioned odor aversions generalize to tastants, and whether conditioned taste aversions generalize to odorants. It will also be examined whether prior odor-taste pair experience is necessary for generalization to occur and whether the specificity of the generalization follows this learned taste-odor quality congruence. A separate study will investigate the flavor experience-dependence of the potentiation of an odor aversion by taste and of a taste aversion by odor. To determine whether multi-sensory integration occurs in the olfactory bulb, the third study will evaluate whether and how oral stimuli can modulate odor responses in the optically-imaged olfactory bulb of awake and acute rats. The importance of both stimulus quality congruence, as established by modulating flavor experience, and temporal congruence for flavor integration will also be assessed. Together these studies are intended to provide fundamentally new knowledge about the neural mechanisms of flavor perception using a rat model. PUBLIC HEALTH RELEVANCE: This project investigates the neural basis of flavor perception. Because flavor plays a central role in motivating food intake, research on the neural mechanisms of flavor perception is essential for understanding the sensory factors that contribute to eating-related disorders such as obesity, diabetes and cardiovascular disease.